ABSTRACT Diabetes is the leading cause of nontraumatic lower extremity amputations in the United States. Diabetic foot ulcers (DFUs) are responsible for more hospitalizations than any other diabetic complications. Currently, even the best available treatments achieve only a 50% healing rate for these wounds?and this healing is often only temporary, with a 66% chance of recurring. Our company has developed an intracellular ATP delivery technique (ATP-vesicles or VitaSolTM) for tissue ischemia. When used in wound treatment, it heals wounds faster than many control dressings. During the Phase I period, VitaSolTM healed wounds faster than Regranex and showed no toxic effects in the local lymph nodes or reproductive systems in both male and female rabbits. One special feature of VitaSolTM is its ability to trigger extremely rapid tissue regeneration?granulation growth appears within 24 hours after application. This growth continues and covers the wound cavity within a few days?a phenomenon never seen or reported before with any other treatment strategy. The Phase II study will bring this new technique closer from the bench to bedside. We will first undertake a larger scale manufacturing of VitaSolTM in a cGMP facility to meet FDA requirements, and to produce VitaSolTM in a practical package for easy application. We will then test the new VitaSolTM preparation in an animal model close to DFU (12-month diabetes plus ischemia) and to compare the healing effects with Regranex. Our approach is a potential game changer for DFU treatment: The wound healing process involves hemostasis, inflammation, proliferation, and remodeling resulting in a 3?6 day lag before granulation tissue starts to appear. This process seems to be ?carved in stone? and no one has ever been able to change it. The elimination of the lag time, and the ability to support cell survival and proliferation in a wound cavity without blood supply, are two features never been achieved with any other treatment. These characteristics could have tremendous potential in the treatment of DFUs. The potential impact is high.